Category Archives: Physiology

A UO-led team of researchers spanning physics, neuroscience, molecular biology, ecology and evolution will use a new $325,000 grant to examine aquatic symbioses the interactions between different animal species living together.

The project is funded by a 30-month award from the Gordon and Betty Moore Foundation and involves the study of zebrafish in controlled ecosystems.

The team will leverage decades worth of pioneering research at the UO involving zebrafish and explorations of the gut microbiome, in which vast numbers of microbes contribute to both health and disease in their hosts. UO has been a leader in zebrafish research since the 1960s, when the late biologist George Streisinger established zebrafish as an ideal model for studying human development and disease.

We aim to develop new tools for studying these symbioses throughout the entire lifespan of zebrafish, which serves as a model aquatic animal and a model for phenomena relevant to all vertebrates, including humans, said Raghuveer Parthasarathy, an Alec and Kay Keith Professor in the Department of Physics, a member of the UOs Institute of Molecular Biology and Materials Science Institute, and the principal investigator on the award.

The project builds on the successes of the zebrafish group here at the UO and it pushes it to the next frontier of trying to capture the whole lifespan of the animal and its ecosystem, Parthasarathy said.

Along with Parthasarathy, the team includes Karen Guillemin, Judith Eisen and Brendan Bohannan, all professors in the Department of Biology. Guillemin is a Philip H. Knight Chair and a member of the Institute of Molecular Biology. Eisen is a member of the Institute of Neuroscience. Bohannan, the James F. and Shirley K. Rippey Chair in Liberal Arts and Sciences, is a member of the Institute of Ecology and Evolution.

The team also includes John Rawls, a professor of molecular genetics and microbiology at Duke University and the director of the Duke Microbiome Center.

Part of the Moore Foundations Symbiosis in Aquatic Systems Initiative, the project will contribute to a larger effort to equip the scientific community with new genetic tools, cultivation methods and other infrastructure to improve experimental capabilities in aquatic symbiosis research over the coming decade. Increasingly, researchers are recognizing that symbiotic bacteria are critical components in the processes that sculpt the evolution, ecology, development and physiology of animals, yet remarkably little is known about exactly how those processes play out.

The four UO researchers have worked together on previous projects as part of the UOs interdisciplinary Microbial Ecology and Theory of Animals, a National Institutes of Health-funded Center of Excellence in Systems Biology. The center is funded by a $7.6 million grant and seeks to better understand the bacteria and other microorganisms that reside in the animal gut and influence many biological functions.

Building on their earlier work studying individual biological processes, the new research will explore the entire ecosystem and lifespan of zebrafish and consider food chains, population densities and other attributes. The project will serve as a bridge between more traditional model system research and field studies, opening up new frontiers in zebrafish research, Parthasarathy said.

The project involves three main areas. Investigators will:

Were hoping to learn how can we both predict and control ecosystem constituents, things like food and bacteria and how can that give us healthy organisms throughout their lifespan, Parthasarathy said. Our approach focuses especially on better understanding nutrition and on engineering new aquatic habitats that allow controlled investigation of symbiotic interactions. We want to watch and learn from the entire process.

The UO team will be building on a strong foundation of zebrafish research. That includes groundbreaking work by Eisen examining interactions between the nervous system, immune system and bacteria in the gut, and Guillemins innovative development of specialized sterile zebrafish that allow scientists to better determine the role microbes play as animals grow.

Bohannan has conducted important research on zebrafish, tracking them throughout their life cycle to see how diet, genetics and immune response affect their microbial diversity. And Parthasarathy has employed physics to better understand how gut microbes move and interact with each other, producing stunning, high-resolution, three-dimensional images and videos of gut bacteria in zebrafish using a technique known as light sheet microscopy.

Rawls, the biologist from Duke University, studies gut bacteria in zebrafish and their role in regulating digestive physiology, innate immunity and gut-brain communication.

I think (this research) may open up a lot of ecological questions, Parthasarathy said. If we succeed, we can expand our methods to other species such as plants and algae and explore their interactions. I think there is lots of potential for growth.

The project is the latest in a string of awards to UO researchers from the Moore Foundation. Earlier this year Eisen received a $2 million grant through the same symbiosis initiative to probe the relationship between symbiotic bacteria and neural development, using zebrafish as a model organism. In January, UO biologist Kelly Sutherland received a $1.1 million grant from the foundation funding her research examining the swimming mechanisms of gelatinous marine organisms.

These awards are a testament to the exceptional research being conducted at the University of Oregon, said Provost and Senior Vice President Patrick Phillips. We are grateful to the Gordon and Betty Moore Foundation for their generous support of our researchers and their investment in these innovative and impactful projects, which support the foundations critical mission of fostering pathbreaking scientific discovery and further the UOs commitment to enriching the human condition through creative inquiry and scientific discovery.

By Lewis Taylor, University Communications

Physiology

Antibody drugs could be key tools against Covid-19. But will they matter? – STAT

August 11, 2020 medical

From the moment Covid-19 emerged as a threat, one approach to making drugs to treat or prevent the disease seemed to hold the most promise: Theyre known as monoclonal antibodies.

Now, scientists are on the brink of getting important data that may indicate whether these desperately needed therapies could be safe and effective. Clinical trials involving a pair of antibodies developed by Regeneron Pharmaceuticals will read out early results in September. A separate effort from Eli Lilly could yield data later in the fall.

Despite experts eagerness to see the data, however, there remains a debate over just how significant a role any antibody treatment might play in changing the course of the pandemic.

A lot of smart people who understand immunology and virology think antibodies will work, said Robert Nelsen, an investor at ARCH Venture Partners who is invested in Vir Biotechnology, which will start tests of its own Covid-19 antibody study this month.

Scott Gottlieb, the former commissioner of the Food and Drug Administration, is less sure antibody treatments will be significant factors in bringing the pandemic under control. Even though the development efforts have been proceeding extraordinarily fast by normal standards, the U.S. has spent billions of dollars purchasing vaccines in advance, but has done far less to shore up capacity for antibody drugs.

We may have missed a window to scale the manufacturing of antibody drugs that could have been an important bridge to a vaccine and a hedge in the event vaccines are delayed or dont work, Gottlieb, a fellow at the American Enterprise Institute and board member for Pfizer and other health care companies, told STAT. These drugs had the ability to perhaps meaningfully change the contours of this epidemic, and we just wont have enough doses to realize that goal.

Monoclonal antibodies are antibodies the kind that the body produces to neutralize invading viruses that have been genetically engineered into new medicines.

In 1975, two researchers, Georges J.F. Khler and Csar Milstein, developed the method for mass-producing them by fusing antibody-producing cells from mice with cancer cells. They shared the Nobel Prize in physiology or medicine in 1984. The first monoclonal antibody drug, for kidney transplant patients, was approved in 1986. Today, Humira, an antibody from AbbVie that treats a host of immune-related diseases, is the pharmaceutical industrys top-selling product, generating $15 billion in sales last year.

Regeneron has produced several monoclonal antibodies since being founded in 1988, including Praluent for high cholesterol, Libtayo for a type of cancer, and Dupixent for severe eczema. In 2014, the technology was also used to develop an effective treatment for Ebola.

As the Covid pandemic hit, Regenerons chief scientific officer, George Yancopoulos, assigned Christos Kyratsous, a confident, Porsche-driving scientist with a dry sense of humor, to lead a team that would search for an antibody. In early February, a non-infectious fragment of genetic code of the novel coronavirus arrived at the companys research laboratories in Tarrytown, N.Y., from China, and the company has used this starting material to produce hundreds of virus-neutralizing antibodies using genetically engineered mice, along with blood taken from survivors of Covid-19.

But getting antibodies into people has taken time. I tragically right now have a 91-year-old aunt whos trapped in a nursing home where right now theres a coronavirus outbreak, Yancopoulos said in April. And I just wish I could get them our [drug] today. Its just not ready.

Other companies are advancing their own efforts. For years, AbCellera, a Vancouver-based biotech, had been working with the National Institutes of Health and the U.S. Department of Defense to game out the response to future pandemics. In February, the NIHs National Institute of Allergy and Infectious Diseases sent the company a sample of blood from a patient who had recovered from Covid-19. AbCellera inserted the sample into a credit-card-sized device that isolates the B cells that make antibodies, and used it to find more than 550 antibodies that might work against the virus.

Adaptive Biotechnologies, AbbVie, and AstraZeneca have also rushed forward with their own antibody efforts.

Regenerons antibodies REGN10933 and REGN10987 both target the spike protein on the virus surface that helps it invade cells, but individually, each drug binds to the protein at a different, non-overlapping location. This cocktail approach aims to increase the chance that the virus can be neutralized without escaping. Its the same multidrug strategy used successfully to treat other viral diseases such as HIV and hepatitis C. Regeneron refers to the dual antibody regimen as REGN-COV2.

The first look at Regenerons data will provide results on the ability of REGN-COV2 to reduce the amount of SARS-CoV-2 virus in patients compared to placebo. Safety and other data will also be announced.

Outcomes data will come later. For the study of hospitalized Covid-19 patients, Regeneron hopes to show that the treatment can improve clinical status based on a seven-point scale ranging from hospital discharge to death. In between, the scoring system measures changes in the use of supplemental oxygen or mechanical ventilation. In the study of ambulatory Covid-19 patients, REGN-COV2 is designed to speed recovery and prevent the disease from getting worse. Unlike Regeneron, Eli Lilly and AbCellera have chosen not to use a cocktail approach, starting instead by testing a single antibody. Data from its study, however, being conducted with the NIH, arent expected to be released until October or November.

Reducing the theoretical risk of escape mutations has a real cost, and the real cost is manufacturing, meaning you will have less doses available, meaning fewer people will be treated in this critical time period, Lilly Chief Scientific Officer Daniel Skovronsky told STAT during a recent event. So my view is we go for a single antibody, which means that we can treat twice as many people if it works.

The Lilly antibody, called LY-CoV555, will be investigated in a placebo-controlled clinical trial of approximately 300 patients hospitalized with mild to moderate Covid-19. An initial efficacy assessment based on symptoms improvement, including the need for supplemental oxygen, will be conducted five days following the injections of LY-CoV555 or placebo. If these initial results show a benefit for the Lilly antibody, the study will be expanded to enroll another 700 patients, including people with severe cases of Covid-19.

Recently published animal data suggest these antibody treatments may work in humans. Monkeys exposed to SARS-CoV-2 followed one day later with injections of the Regeneron cocktail cleared the virus faster than monkeys treated with a placebo. Damage to the lungs, including cases of pneumonia, was reduced but not eliminated in the monkeys treated with the cocktail compared to the placebo group. The monkey study was released via a preprint server, meaning the data had not yet been peer-reviewed or published in a journal.

In a research note, SVB Leerink analyst Geoff Porges called the monkey data quite encouraging, but he also cautioned it may not be curative in humans on its own, citing the inconclusive pneumonia results and the challenge of treating patients early, before they might have symptoms.

If clinical development for the antibody cocktails is successful, we believe it would be most likely to complement the existing standard of care and antiviral therapies such as remdesivir, rather than displacing antivirals, said Porges.

Nelsen, the investor at ARCH Venture Partners, said: If you treat people who are very sick, you may not see anything. If you treat people earlier, you will probably see what you saw in the monkeys: a significant reduction in virus, which doesnt necessarily mean a reduction in morbidity and mortality, but it should. What you really want to do is prevent the progression of the disease.

Vir, the biotech firm that Nelsen backed, will start a clinical trial of its lead antibody candidate VIR-7831 later this month, seeking to show that it can prevent hospitalization due to Covid-19. A second antibody candidate, VIR-7832, will advance into a clinical trial later this year. Both drugs are designed to bind to a location on the spike protein that creates a high barrier to resistance. In preclinical studies, the antibodies also recruit immune cells to help kill other cells already infected by the virus, Vir said.

Similar to vaccines, antibody treatments are also being developed to prevent Covid-19 infection, particularly in people who are at high risk and who might have been exposed to the virus through close contact with an already infected person.

Once someone has come into contact with some of the disease, its too late for an active vaccine, Lillys Skovronsky said. But a passive immunization like our antibody could be valuable. When you think about the populations that are suffering the most, its the elderly, its the immunocompromised, its patients in nursing homes and long-term care facilities.

Lilly and NIAID are conducting a 2,400-patient Phase 3 study to test whether its treatment can keep nursing home patients from developing Covid-19. The antibody will be given to patients and staff at places where there has been an infection to see if it can stop them from developing the disease. To conduct the study, Lilly is deploying a fleet of recreational vehicles that can be used prepare study drug and do lab work, as well as pull trailers that can be used as on-site infusion clinics.

Regeneron and NIAID are also conducting a prevention study in 2,000 healthy adults who are household contacts with an individual with a positive Covid-19 test. Will it be possible to manufacture enough antibody? Regeneron said it is in active discussions with other parties that can add additional manufacturing capacity.

The big determinant of how fast answers will emerge will be the speed at which doctors can enroll patients in these studies, said Anita Kohli, the director of clinical research at Arizona Clinical Trials and an investigator for both Regeneron and Eli Lilly. This, she said, is harder than it sounds, especially for patients who are not so sick that they are in the hospital. I think some of the recruitment is more difficult, because youre recruiting sick people, she said. Sick people want to eat chicken soup and stay at home and not go to the clinical trials center.

One problem is that diagnostic tests are taking a long time to come back. Doctors are supposed to enroll patients in the studies within five or six days of the onset of symptoms. If testing takes two weeks to come back, patients often recover before they are enrolled. Kohlis center has begun to test patients for Covid in the hopes that some will volunteer to be in studies.

Vaccines are not going to work for everybody, she said. People are still going to get sick, theres no two ways about it. And weve got to have a treatment.

The problem, she said, is that patients are not being made aware of clinical trials for therapeutics soon enough.

People have not been directed toward clinical trials, or are not thinking about them, she said. I think thats what we need to change here. Its not that they arent very exciting, they are very exciting. They just arent talked about enough.

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Antibody drugs could be key tools against Covid-19. But will they matter? - STAT

Physiology

The Secret to a Long, Healthy Life Is in the Genes of the Oldest Humans Alive – Singularity Hub

August 10, 2020 medical

The first time I heard nematode worms can teach us something about human longevity, I balked at the idea. How the hell can a worm with an average lifespan of only 15 days have much in common with a human who lives decades?

The answer is in their genesespecially those that encode for basic life functions, such as metabolism. Thanks to the lowly C. elegans worm, weve uncovered genes and molecular pathways, such as insulin-like growth factor 1 (IGF-1) signaling that extends healthy longevity in yeast, flies, and mice (and maybe us). Too nerdy? Those pathways also inspired massive scientific and popular interest in metformin, hormones, intermittent fasting, and even the ketogenic diet. To restate: worms have inspired the search for our own fountain of youth.

Still, thats just one success story. How relevant, exactly, are those genes for humans? Were rather a freak of nature. Our aging process extends for years, during which we experience a slew of age-related disorders. Diabetes. Heart disease. Dementia. Surprisingly, many of these dont ever occur in worms and other animals. Something is obviously amiss.

In this months Nature Metabolism, a global team of scientists argued that its high time we turn from worm to human. The key to human longevity, they say, lies in the genes of centenarians. These individuals not only live over 100 years, they also rarely suffer from common age-related diseases. That is, theyre healthy up to their last minute. If evolution was a scientist, then centenarians, and the rest of us, are two experimental groups in action.

Nature has already given us a genetic blueprint for healthy longevity. We just need to decode it.

Long-lived individuals, through their very existence, have established the physiological feasibility of living beyond the ninth decade in relatively good health and ending life without a period of protracted illness, the authors wrote. From this rare but valuable population, we can gain insight into the physiology of healthy aging and the development of new therapies to extend the human healthspan.

While it may seem obvious now, whether genes played a role in longevity was disputed for over a century. After all, rather than genes, wouldnt access to health care, socioeconomic status, diet, smoking, drinking, exercise, or many other environmental and lifestyle factors play a much larger role? Similar to height or intelligence (however the latter is assessed), the genetics of longevity is an enormously complicated and sensitive issue for unbiased studying.

Yet after only a few genetic studies of longevity, a trend quickly emerged.

The natural lifespan in humans, even under optimal conditions in modern societies, varies considerably, the authors said. One study, for example, found that centenarians lived much longer than people born around the same time in the same environment. The offspring of centenarians also have lower chances of age-related diseases and exhibit a more youthful profile of metabolism and age-related inflammation than others of the same age and gender.

Together, about 25 to 35 percent of the variability in how long people live is determined by their genesregardless of environment. In other words, rather than looking at nematode worm genes, we have a discrete population of humans whove already won the genetic lottery when it comes to aging. We just need to parse what winning means in terms of biology. Genes in hand, we could perhaps tap those biological phonelines and cut the wires leading to aging.

Identification of the genetic factors that underlie extreme human lifespan should provide insights into the mechanisms of human longevity and disease resistance, the authors said.

Once scientists discovered that genes play a large role in aging, the next question was which ones are they?

They turned to genome-wide association studies, or GWAS. This big data approach scans existing genomic databases for variations in DNA coding that could lead to differences in some outcomefor example, long versus short life. The differences dont even have to be in so-called coding genes (that is, genes that make proteins). They can be anywhere in the genome.

Its a powerful approach, but not that specific. Think of GWAS as rudimentary debugging software for biological code: it only looks for differences between different DNA letter variants, but doesnt care which specific DNA letter swap most likely impacts the final biological program (aging, in this case).

Thats a huge problem. For one, GWAS often finds dozens of single DNA letter changes, none powerful enough to change the trajectory of aging by itself. The technique highlights a village of DNA variants, that together may have an effect on aging by controlling the cells course over a lifetime, without indicating which are most important. Its also hard to say that a DNA letter change causally leads to (or protects against) aging. Finally, GWAS studies are generally performed on populations of European ancestry, which leaves out a huge chunk of humansfor example, the Japanese, who tend to produce an outsized percentage of centenarians.

So what needs to change?

Rather than focusing on the general population, the key is to home in on centenarians of different cultures, socioeconomic status, and upbringing. If GWAS are like fishing for a rare species in several large oceans, then the authors point is to focus on pondsdistributed across the worldwhich are small, but packed with those rare species.

Extremely long-lived individuals, such as centenarians, compose only a tiny proportion (~0.01 percent to 0.02 percent) of the United States population, but their genes contain a biological blueprint for healthy aging and longevity, the authors said. Theyre spared from usual age-related diseases, and this extreme and extremely rare phenotype is ideal for the study of genetic variants that regulate healthspan and lifespan.

Its an idea that would usually make geneticists flinch. Its generally thought that the larger the study population, the better the result. Here, the recommendation is to narrow our focus.

And thats the point, the authors argue.

Whatever comes out of these studies will likely have a much larger impact on aging than a GWAS fishing experiment. Smaller (genomic) pond; larger (pro-youth) fish. Whats more, a pro-youth gene identified in one European-based long-living population can be verified in another group of centenarianssay, Japaneseensuring that the gene candidates reflect something fundamental about human aging, regardless of race, culture, upbringing, and wealth.

A genomic screen of centenarians can easily be done these days on the cheap. But thats only the first step.

The next step is to validate promising anti-aging genetic differences, similar to how scientists validated such differences in nematode worms during classic longevity studies. For example, a promising pro-youth gene variant can be genetically edited into mice using CRISPR or some other tool. Scientists can then examine how the mice grow up and grow old, compared to their non-edited peers. Does the gene make these mice more resilient to dementia? What about muscle wasting? Or heart troubles? Or hair greying and obesity?

From these observations, scientists can then use an enormous selection of molecular tools to further dissect the molecular pathways underlying these pro-youth genetic changes.

The final step? Guided by centenarian genes and validated by animal models of aging, we can design powerful drugs that sever the connection between the genes and proteins that drive aging and its associated diseases. Metformin is an experimental pill that came out of aging studies in nematode wormsimagine what studies in human centenarians will yield.

Despite enormous improvements in human health over the past century, we remain far from a situation in which living to 100 years of age in fairly good health is the norm, the authors said.

But as centenarians obviously prove, this is possible. By digging into their genes, scientists may find a path towards healthy longevitynot just for the genetically fortunate, but for all of us.

Image credit:Cristian Newman / Unsplash

Physiology

Impact of delayed ventricular wall area ratio on pathophysiology of mechanical dyssynchrony: implication from single-ventricle physiology and 0D…

August 10, 2020 medical

This article was originally published here

J Physiol Sci. 2020 Aug 6;70(1):38. doi: 10.1186/s12576-020-00765-y.

ABSTRACT

Electrical disparity can induce inefficient cardiac performance, representing an uncoordinated wall motion at an earlier activated ventricular wall: an early shortening followed by a systolic rebound stretch. Although regional contractility and distensibility modulate this pathological motion, the effect of a morphological factor has not been emphasized. Our strain analysis in 62 patients with single ventricle revealed that those with an activation delay in 60-70% of ventricular wall area suffered from cardiac dysfunction and mechanical discoordination along with prolonged QRS duration. A computational simulation with a two-compartment ventricular model also suggested that the ventricle with an activation delay in 70% of the total volume was most vulnerable to a large activation delay, accompanied by an uncoordinated motion at an earlier activated wall. Taken together, the ratio of the delayed ventricular wall has a significant impact on the pathophysiology due to an activation delay, potentially highlighting an indicator of cardiac dysfunction.

PMID:32762655 | DOI:10.1186/s12576-020-00765-y

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Impact of delayed ventricular wall area ratio on pathophysiology of mechanical dyssynchrony: implication from single-ventricle physiology and 0D...

Physiology

Professor Horace Barlow, neuroscientist who did groundbreaking work on visual perception obituary – Telegraph.co.uk

August 10, 2020 medical

Following the outbreak of war, he went up to Trinity College, Cambridge, as a medical student, though he technically read Natural Sciences, which was the normal thing for medical students at Cambridge at the time.

He won a Rockefeller studentship to finish his clinical studies at Harvard Medical School, where he went after spending a year at the Medical Research Councils lab in London at Mount Vernon, working on problems of diving in relation to the war.

It was at Harvard that, with two fellow medical students, he first carried out research on vision, publishing papers on the effect of magnetic fields on the eye and on dark adaptation and light effects on the electric threshold of the eye.

By the time he returned to Britain, although he completed his medical training at University College Hospital, London, it was clear that he wanted to continue as a research neurophysiologist, and he returned to Cambridge to study Neurophysiology under Edgar (later Lord) Adrian.

Barlow was a fellow at Trinity College (1950-54), and a Fellow and lecturer in Physiology at Kings College, Cambridge (1954-64). In 1964 he crossed the Atlantic to take up an appointment as Professor of Physiology at the University of California, Berkeley.

There he researched many aspects of the physiology and psychology of vision, much of it in collaboration with Bill Levick. Among other things, he discovered that certain retinal cells fire signals when light passes over them in one direction but not in the opposite direction a discovery which stimulated enduring interest in the cellular mechanism behind this directional selectivity, which is now seen as the basis of motion perception.

Later, working with Colin Blakemore and Jack Pettigrew, Barlow discovered the brains mechanism of stereo vision by showing that signals from the two eyes converge on single cells in the visual cortex that respond to specific locations in 3D space.

In 1973 he returned to Cambridge, where he was Royal Society Research Professor of Physiology with a fellowship at Trinity College.

Soft-spoken, but resolute in his opinions and endlessly curious about the natural world, Barlow continued to write about the brain, working in his department and visiting Trinity well into his nineties. His definition of intelligence was the art of good guessing. He continued to be a presence at national and international meetings, taking great pleasure in meeting and educating younger scientists. He supervised the training of more than a dozen doctoral and postdoctoral students, and exerted a broad influence on thinking in the field through their influence as well as his own.

Barlow was elected a Fellow of the Royal Society in 1969 and was awarded the Societys Royal Medal in 1993. In the same year he received the Australia Prize. He won the 2009 Swartz Prize from the Society for Neuroscience and the first Ken Nakayama Prize from the Vision Sciences Society in 2016.

Barlow married first, in 1954, Ruthala Salaman. The marriage was dissolved in 1970, and in 1980 he married, secondly, Miranda Weston-Smith, who survives him with their two daughters and a son, and four daughters from his first marriage.

Professor Horace Barlow, born December 8 1921, died July 5 2020

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Professor Horace Barlow, neuroscientist who did groundbreaking work on visual perception obituary - Telegraph.co.uk

Physiology

Community support urged for breastfeeding moms and babies – Press Publications Inc.

August 10, 2020 medical

August is National and World Breastfeeding Awareness Month, and on Aug. 1, Ohio. Gov. Mike DeWine and Lt. Gov. Jon Husted signed a proclamation that Ohio is joining in the observance. The State of Ohio joins the Surgeon General and the United States Breastfeeding Committee in the belief that Ohio breastfeeding rates will improve if social policy and community norms support breastfeeding mothers and babies, the proclamation said. For this years Breastfeeding Awareness Month, Ohio has adopted the theme, Support Breastfeeding for a Healthier Planet. This theme focuses on the impact of infant feeding on the environment and climate change and the imperative to protect, promote and support breastfeeding for the health of the planet and its people. The American Academy of Pediatrics and the World Health Organization recommend exclusive breastfeeding for the first six months of life and continued breastfeeding with the addition of appropriate solid food for the first year and beyond. The U.S. Centers for Disease Control and Prevention report that Ohios 2018 breastfeeding initiation rate of 81.9 percent ranks 36th in the nation. The CDC also states that rates of breastfeeding duration and exclusivity are lower among Black infants than among white infants. Increasing rates of breastfeeding initiation and supporting continuation of breastfeeding among Black women might help reduce disparities in breastfeeding duration. Strategies may include improving peer and family support, access to evidence-based maternity care, and employment support. In light of the financial and life-saving benefits of breastfeeding, all elements of the Wood County community must cooperate and support breastfeeding, said Jackie Mears, Wood County WIC (Women, Infants and Children) Director. Ultimately our whole society benefits from having healthier mothers, babies and children when breastfeeding is promoted, protected and supported. While breastfeeding is a personal choice, communities play a vital role in informing and supporting a mothers decision to breastfeed her baby, Mears said, adding that returning our communities to a breastfeeding supportive culture will take efforts by family, friends, employers, educational institutions, hospitals and businesses. The Wood County Health Department offers these suggestions for improving social policy and community norms to support breastfeeding mothers and babies.: Businesses and the community members can help mothers feel comfortable nursing in public. Hungry babies need to eat, and Ohio law allows breastfeeding in public. Businesses can show their support by placing the Breastfeeding Welcome Here universal sign for breastfeeding in their windows and educating their staff on the acceptance of breastfeeding in their establishments. Employers can also encourage employees and provide a private space (other than a bathroom) to pump. This will increase employee retention and reduce medical costs. Hospitals can adopt the Ten Steps to Successful Breastfeeding as an indication that they are dedicated to supporting new mothers who choose to breastfeed. Educational institutions can support breastfeeding by presenting age-appropriate education on the anatomy and physiology of the human body. Breastfeeding mothers can reach out through groups and chatrooms on social media to get the support they need. For more information about breastfeeding, contact a member of the Wood County WIC Breastfeeding Team at 419-354-9661 or adonaldson@co.wood.oh.us. The mission of Wood County Health Department is to prevent disease, promote healthy lifestyles and protect the health of everyone in Wood County. The departments Community Health Center provides comprehensive medical services for men, women and children. All patients are welcome, including uninsured or underinsured clients, regardless of their ability to pay. Most third-party insurance is accepted. Visit http://www.WoodCountyHealth.org for more details.

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Community support urged for breastfeeding moms and babies - Press Publications Inc.

Physiology

Pizza Study Shows Body’s Resilience to ‘Pigging Out’ – HealthDay News

August 10, 2020 medical

FRIDAY, Aug. 7, 2020 (HealthDay News) -- Ever felt guilty for that occasional binge on high-calorie, fatty foods?

Relax: A new study of folks overindulging on pizza finds that if you're healthy and you don't 'pig out' regularly, your body deals with it just fine.

British researchers looked at the effects of eating until not just full, but so full that the participants could not take another bite. Then, they tested the blood of the 14 healthy young men who participated in the study to determine whether there were any changes in blood sugar, blood fats, insulin and other hormones.

The team discovered that even when the men had eaten double the amount of pizza that it would take to make them comfortably full, their blood tests showed no negative consequences.

"I think that's the really remarkable thing here, that we have a huge capacity to overeat and, despite that huge capacity, the body does really quite well at controlling blood sugars and blood fat after that meal," said study author James Betts, a professor of metabolic physiology at the University of Bath's Centre for Nutrition, Exercise and Metabolism.

Betts said it was notable both that the body's response kept blood sugar and lipids under control after such a big meal, and that it was possible for participants to consume so much excess food.

When eating until full, they averaged the equivalent of a large pizza. When eating until maximally full, they ate about two large pizzas, Betts said.

"We expected people to eat more when they were asked to go beyond full, but we expected that to be slightly more," Betts said. "We were really amazed that it was almost exactly 100% more."

The study was published online recently in the British Journal of Nutrition.

Betts and one of his co-authors stumbled upon the idea for the study while traveling to a conference. The only open airport restaurant was a McDonald's, so they each got a McMuffin breakfast sandwich.

"We ate those and enjoyed them and said, 'Oh, I could eat another one,'" Betts said. "That prompted a discussion of 'How many do you think you could eat?' and 'What would be the physiological responses to eating more and more?'"

While researching during the long flight, they discovered there had been no previous studies about eating beyond full, Betts said.

They chose pizza because it tastes good, so people would keep eating. Its high fat and carbohydrate content offered a big challenge to the body, Betts said.

Typically, blood sugar and blood lipids increase in response to how much a person eats, Betts said. A small meal will result in fewer changes than a medium meal, for example.

Yet, after overeating, blood sugar was no higher than after a normal meal. Blood lipids such as triglycerides were slightly higher, even though fat consumption was double. Insulin, which is released to control blood sugar, was 50% higher than normal. Hormones that increase feelings of fullness changed the most.

Connie Diekman, a food nutrition consultant in St. Louis, said the study documents what scientists already understand about the body and its ability to process food. Sometimes people get confused when wondering whether they are eating right, should consume fewer carbs, eat fewer fats or should try something like a Keto diet or intermittent fasting, Diekman said.

"I think it does demonstrate very nicely that our body knows what to do with the food we eat. It knows how to fuel us well," Diekman said.

Of course, Diekman added, constant overeating would challenge how well insulin can do its job and how well the body can move fat without having a lingering impact on blood lipids. This shows that it's OK to have a larger meal for a special occasion, she said.

"You should enjoy the meal," Diekman said, "and then you get back to your regular eating plan."

The study was limited to individuals who were healthy and lean. They ranged in age from 24 to 37. Only men volunteered. A future study may look at the impact of overeating on people who are overweight or have health issues, Betts said.

Though a one-time indulgent meal appears to be fine for a healthy person, Betts said that he hopes the message is clear that this isn't meant for people who are unhealthy or for indulging all the time.

"If you've got a diet that is already really very healthy and an active lifestyle to go with it, then these overindulgences can be even more frequent without imbalancing everything else," Betts said. "How often is too often really comes down to wider choices in the lifestyle."

More information

There's more on eating healthy at the U.S. Centers for Disease Control and Prevention.

SOURCES: James Betts, Ph.D., professor, metabolic physiology, Centre for Nutrition, Exercise and Metabolism, University of Bath, England; Connie Diekman, M.Ed., R.D., L.D., food nutrition consultant, St. Louis; British Journal of Nutrition, April 6, 2020, online

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Pizza Study Shows Body's Resilience to 'Pigging Out' - HealthDay News

Physiology

Brain scientists haven’t been able to find major differences between women’s and men’s brains, despite over a century of searching – The Conversation…

August 10, 2020 medical

People have searched for sex differences in human brains since at least the 19th century, when scientist Samuel George Morton poured seeds and lead shot into human skulls to measure their volumes. Gustave Le Bon found mens brains are usually larger than womens, which prompted Alexander Bains and George Romanes to argue this size difference makes men smarter. But John Stuart Mill pointed out, by this criterion, elephants and whales should be smarter than people.

So focus shifted to the relative sizes of brain regions. Phrenologists suggested the part of the cerebrum above the eyes, called the frontal lobe, is most important for intelligence and is proportionally larger in men, while the parietal lobe, just behind the frontal lobe, is proportionally larger in women. Later, neuroanatomists argued instead the parietal lobe is more important for intelligence and mens are actually larger.

In the 20th and 21st centuries, researchers looked for distinctively female or male characteristics in smaller brain subdivisions. As a behavioral neurobiologist and author, I think this search is misguided because human brains are so varied.

The largest and most consistent brain sex difference has been found in the hypothalamus, a small structure that regulates reproductive physiology and behavior. At least one hypothalamic subdivision is larger in male rodents and humans.

But the goal for many researchers was to identify brain causes of supposed sex differences in thinking not just reproductive physiology and so attention turned to the large human cerebrum, which is responsible for intelligence.

Within the cerebrum, no region has received more attention in both race and sex difference research than the corpus callosum, a thick band of nerve fibers that carries signals between the two cerebral hemispheres.

In the 20th and 21st centuries, some researchers found the whole corpus callosum is proportionally larger in women on average while others found only certain parts are bigger. This difference drew popular attention and was suggested to cause cognitive sex differences.

But smaller brains have a proportionally larger corpus callosum regardless of the owners sex, and studies of this structures size differences have been inconsistent. The story is similar for other cerebral measures, which is why trying to explain supposed cognitive sex differences through brain anatomy has not been very fruitful.

Even when a brain region shows a sex difference on average, there is typically considerable overlap between the male and female distributions. If a traits measurement is in the overlapping region, one cannot predict the persons sex with confidence. For example, think about height. I am 57". Does that tell you my sex? And brain regions typically show much smaller average sex differences than height does.

Neuroscientist Daphna Joel and her colleagues examined MRIs of over 1,400 brains, measuring the 10 human brain regions with the largest average sex differences. They assessed whether each measurement in each person was toward the female end of the spectrum, toward the male end or intermediate. They found that only 3% to 6% of people were consistently female or male for all structures. Everyone else was a mosaic.

When brain sex differences do occur, what causes them?

A 1959 study first demonstrated that an injection of testosterone into a pregnant rodent causes her female offspring to display male sexual behaviors as adults. The authors inferred that prenatal testosterone (normally secreted by the fetal testes) permanently organizes the brain. Many later studies showed this to be essentially correct, though oversimplified for nonhumans.

Researchers cannot ethically alter human prenatal hormone levels, so they rely on accidental experiments in which prenatal hormone levels or responses to them were unusual, such as with intersex people. But hormonal and environmental effects are entangled in these studies, and findings of brain sex differences have been inconsistent, leaving scientists without clear conclusions for humans.

While prenatal hormones probably cause most brain sex differences in nonhumans, there are some cases where the cause is directly genetic.

This was dramatically shown by a zebra finch with a strange anomaly it was male on its right side and female on its left. A singing-related brain structure was enlarged (as in typical males) only on the right, though the two sides experienced the same hormonal environment. Thus, its brain asymmetry was not caused by hormones, but by genes directly. Since then, direct effects of genes on brain sex differences have also been found in mice.

Many people assume human brain sex differences are innate, but this assumption is misguided.

Humans learn quickly in childhood and continue learning alas, more slowly as adults. From remembering facts or conversations to improving musical or athletic skills, learning alters connections between nerve cells called synapses. These changes are numerous and frequent but typically microscopic less than one hundredth of the width of a human hair.

Studies of an unusual profession, however, show learning can change adult brains dramatically. London taxi drivers are required to memorize the Knowledge the complex routes, roads and landmarks of their city. Researchers discovered this learning physically altered a drivers hippocampus, a brain region critical for navigation. London taxi drivers posterior hippocampi were found to be larger than nondrivers by millimeters more than 1,000 times the size of synapses.

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So its not realistic to assume any human brain sex differences are innate. They may also result from learning. People live in a fundamentally gendered culture, in which parenting, education, expectations and opportunities differ based on sex, from birth through adulthood, which inevitably changes the brain.

Ultimately, any sex differences in brain structures are most likely due to a complex and interacting combination of genes, hormones and learning.

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Brain scientists haven't been able to find major differences between women's and men's brains, despite over a century of searching - The Conversation...

Physiology

NIH researchers reframe dog-to-human aging comparisons – National Institutes of Health

July 9, 2020 medical

News Release

Thursday, July 9, 2020

Comparing epigenetic differences between humans and domestic dogs provides an emerging model of aging.

One of the most common misconceptions is that one human year equals seven dog years in terms of aging. However, this equivalency is misleading and has been consistently dismissed by veterinarians. A recent study, published in the journalCell Systems, lays out a new framework for comparing dog-to-human aging. In one such comparison, the researchers found the first eight weeks of a dogs life is comparable to the first nine months of human infancy, but the ratio changes over time. The research used epigenetics, a process by which modifications occur in the genome, as a biological marker to study the aging process. By comparing when and what epigenetic changes mark certain developmental periods in humans and dogs, researchers hope to gain specific insight into human aging as well.

Researchers performed a comprehensive analysis and quantitatively compared the progression of aging between two mammals, dogs and humans. Scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and collaborators at the University of California (UC) San Diego, UC Davis and the University of Pittsburgh School of Medicine carried out the research.

All mammals experience the same overarching developmental timeline: birth, infancy, youth, puberty, adulthood and death. But researchers have long sought specific biological events that govern when such life stages take place. One means to study such a progression involves epigenetics gene expression changes caused by factors other than the DNA sequence itself. Recent findings have shown that epigenetic changes are linked to specific stages of aging and that these are shared among species.

Researchers focused on one type of epigenetic change called methylation, a process in which molecules called methyl groups are attached to particular DNA sequences, usually parts of a gene. Attaching to these DNA regions effectively turns the gene into the "off" position. So far, researchers have identified that in humans, methylation patterns change predictably over time. These patterns have allowed the creation of mathematical models that can accurately gauge the age of an individual called "epigenetic clocks."

But these epigenetic clocks have only been successful in predicting human age. They do not seem to be valid across species, such as in mice, dogs, and wolves. To see why the epigenetic clocks in these other species differed from the human version, researchers first studied the epigenetic changes over the lifetime of a domestic dog and compared the resultsobtained with humans.

Dogs are a useful model for such comparisons because much of their environment, diet, chemical exposure, and physiological and developmental patterns are similar to humans.

"Dogs experience the same biological hallmarks of aging as humans, but do so in a compressed period, around 10 to 15 years on average, versus over 70 years in humans. This makes dogs invaluable for studying the genetics of aging across mammals, including humans," said Elaine Ostrander, Ph.D., NIH Distinguished Investigator and co-author of the paper.

Dr. Ostrander and her colleagues in Trey Ideker's laboratory at UC San Diego took blood samples from 104 dogs, mostly Labrador retrievers, ranging from four weeks to 16 years of age. They also obtained previously published methylation patterns from 320 people, whose ages ranged from 1 to 103 years. The researchers then studied and compared the methylation patterns from both species.

Based on the data, researchers identified similar age-related methylation patterns, specifically when pairing young dogs with young humans or older dogs with older humans. They did not observe this relationship when comparing young dogs to older humans and vice versa.

The study also found that groups of specific genes involved in development can explain much of the similarity, which had similar methylation patterns during aging in dogs and humans.

"These results suggest that aging can, in part, be explained by a continuum of changes beginning in development," said Dr. Ideker. "The programs of development are expressed incredibly strongly at defined periods when the pup is in the womb and childhood. But equally strongly are systems that clamp down to stop it. In a sense, we are looking at aging as the residual 'afterburn' of those powerful forces."

The researchers also attempted to correlate the human epigenetic clock with dogs, using this as a proxy for converting dog years to human years.

The new formula is more complicated than the "multiply by seven" method. When dogs and humans experience similar physiological milestones, such as infancy, adolescence and aging, the new formula provided reasonable estimates of equivalent ages. For example, by using the new formula, eight weeks in dogs roughly translates to nine months in humans, which corresponds to the infant stage in both puppies and babies. The expected lifespan of senior Labrador retrievers, 12 years, correctly translates to 70 years in humans, the worldwide average life expectancy.

The group acknowledges that the dog-to-human years formula is largely based on data from Labrador retrievers alone. Hence, future studies with other dog breeds will be required to test the formula's generalizability. Because dog breeds have different life spans, the formula may be different among breeds.

Dr. Ostrander noted, "It will be particularly interesting to study long-lived breeds, a disproportionate number of which are small in size, versus breeds with a shorter lifespan, which includes many larger breeds. This will help us correlate the well-recognized relationship between skeletal size and lifespan in dogs."

The study also demonstrates that studying methylation patterns may be a useful method to quantitatively translate the age-related physiology experienced by one organism (e.g., humans) to the age at which physiology in a second organism is most similar (e.g., dogs). The group hopes that such translation may provide a useful tool for understanding aging and identifying ways to maximize healthy lifespans.

"This study, which highlights the relevance of canine aging studies, further expands the utility of the dog as a genetic system for studies that inform human health and biology," said Dr. Ostrander.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research, and training and career development at sites nationwide. Additional information about NHGRI can be found at https://www.genome.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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NIH researchers reframe dog-to-human aging comparisons - National Institutes of Health

Physiology

Lung physiology and immune function could spare children from severe COVID-19 – News-Medical.Net

July 9, 2020 medical

Reviewed by Emily Henderson, B.Sc.Jul 8 2020

Differences in lung physiology and immune function in children could be why they are more often spared from severe illness associated with COVID-19 than adults, according to pediatric and adult physicians at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine, who teamed up to investigate the disparity.

The perspectives paper was recently published in American Journal of Physiology-Lung Cellular and Molecular Physiology.

According to the paper, only about 1.7% of the first 149,082 cases in the U.S. were infants, children, and adolescents younger than 18 years old. Authors noted that children under 18 make up 22% of the U.S. population. Only three pediatric deaths were identified by the Centers for Disease Control and Prevention (CDC) as of April 2020.

"These profoundly decreased rates of symptomatic infection, hospitalization, and death are well beyond statistical significance, require further examination, and may hold the key to identifying therapeutic agents," the authors wrote.

Angiotensin-converting enzyme 2s, called ACE2, are the doors that allow SARS-CoV-2, the novel coronavirus that causes COVID-19, to enter the body's cells. Children naturally have less ACE2 in the lungs than adults.

ACE2 are important for viral entry and there seems to be less of them in children, because they increase with age."

Matthew Harting, MD, MS, assistant professor in the Department of Pediatric Surgery at McGovern Medical School at UTHealth, pediatric surgeon with UT Physicians, and senior author of the paper

Harting is also director of the pediatric ECMO program providing advanced cardiac and respiratory support at Children's Memorial Hermann Hospital.

In addition to fewer ACE2 receptors, the authors note the immune system in children responds to viruses differently than that of adults, leaving less opportunity for severe illness in pediatric patients. There are several different mechanisms behind the differences, including the retention of T-cells in children, which are able to fight off or limit inflammation.

"T-cells have a viral response and also an immune modulator response. In severe cases of adult COVID-19 patients, we've seen that those T-cells are reduced, so the ability to fight the virus is also reduced. In kids, those T-cells seem to be maintained, so they are still able to prevent the virus," said Harry Karmouty-Quintana, PhD, an assistant professor in the Department of Biochemistry and Molecular Biology at McGovern Medical School, and a co-author of the paper.

Lung tissue in children naturally has a higher concentration of regulator T-cells. Patients with higher levels of T-cells also have higher levels of Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor, an anti-inflammatory cytokine.

"IL-10 inhibits the inflammation of other components like IL-6 that are detrimental. Adults tend to experience hyperinflammatory state, where kids do not," Karmouty-Quintana said. "In preclinical studies in mice, IL-10 has also shown to decrease with age."

The paper's findings were made possible through collaboration in a multidisciplinary group made up of pediatric and adult physicians and scientists in pediatric surgery, adult critical care, neonatology, and molecular biology.

"We, as physicians, have been challenged with the question of how to treat COVID-19 and we're learning in real time," said Bindu Akkanti, MD, associate professor of critical care medicine with McGovern Medical School, attending physician in critical care with Memorial Hermann-Texas Medical Center, and a study co-author. "I knew that to figure out the best way to treat adults, we needed to get a team together to get to the bottom of why children were being spared from severe illness related to the virus. So, I reached out to Dr. Karmouty-Quintana and we teamed up with Dr. Harting and two other physicians in the Texas Medical Center to start investigating." Akkanti also sees pulmonary patients at UT Physicians.

"Collaborations like this between adult and pediatric providers are really important and this disease highlights where we can learn a lot when we compare the way it behaves in younger kids with older people," Harting said. "Even now as we're learning about effective treatments, we're seeing younger people handle this disease better than older people. Moving forward, physicians and scientists need multidisciplinary collaboration to continue learning - this is just another step in the right direction to attack this virus."

Krithika Lingappan, MBBS, was the first author of the paper and Jonathan Davies, MD, was a co-author. Both Lingappan and Davies are assistant professors of pediatrics at Baylor College of Medicine and neonatologists with Texas Children's Hospital.

As a result of the collaboration, the team has begun a new study using blood samples from patients in different stages of COVID-19 to continue to understand how to treat the virus and the disparities in disease progression between children and adults.

Source:

Journal reference:

Lingappan, K., et al. (2020) Understanding the age divide in COVID-19: why are children overwhelmingly spared?. American Journal of Physiology - Lung Cellular and Molecular Physiology. doi.org/10.1152/ajplung.00183.2020.

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Lung physiology and immune function could spare children from severe COVID-19 - News-Medical.Net